The research proposed focuses on the effects of sleep on control of pharyngeal patency and chemical feedback controlling breathing. Non-rapid eye movement sleep compromises neural mechanisms that maintain an adequate pharyngeal airway and stabilize breathing so that, if predisposing conditions exist (e.g. narrowing of the pharyngeal lumen or hypoxia), pharyngeal occlusion or periodic breathing results. These sleep-induced changes underlie the increase in pharyngeal resistance in normals and patients with obstructive sleep apnea, and they are responsible for periodic breathing in hypoxic normals and patients with central apnea. To investigate the neural and mechanical factors responsible for pharyngeal closure, we shall visualize the lumen of the naso-, oro- and hypo-pharynx while nasal airway positive pressure is applied during sleep in normals, snorers and patients with obstructive sleep apnea and hypopnea. The luminal area of a collapsible segment will be correlated with static and dynamic pressures during single breath steps in pressure, either down from a relatively high pressure or up from a relatively low pressure. The former provides an estimate of compliance of the passive airway and the latter an estimate of compliance of the active airway. The difference will provide a measure of the net action of pharyngeal muscles under spontaneous conditions. We will correlate this difference with observed activity of the genioglossus, tensor palatini and pharyngeal constrictor. The separate effects of static pharyngeal pressure, lung volume, and flow through a narrowed orifice will be examined. In patients, the site and compliance of the collapsible segment will be correlated with wakeful CT scan estimates of soft- tissue volumes and with the outcome of corrective pharyngeal surgery. Non-obstructive periodic breathing during sleep will be investigated using two approaches. First, the contribution of oscillation of the hypoxia stimulus in hypoxic normals and patients with obstructive and non-obstructive periodic breathing during sleep will be examined by clamping alveolar P02. Second, the importance of hypocapnia will be examined by changing inspired C02 concentration under conditions of mechanically assisted hyperventilation. The results of this project will reveal the contribution of stimulus-response hysteresis in the hypocapnic range.